Prostaglandins mediate the fetal pulmonary response to intrauterine inflammation
نویسندگان
چکیده
Westover AJ, Hooper SB, Wallace MJ, Moss TJM. Prostaglandins mediate the fetal pulmonary response to intrauterine inflammation. Am J Physiol Lung Cell Mol Physiol 302: L664–L678, 2012. First published January 27, 2012; doi:10.1152/ajplung.00297.2011.— Intra-amniotic (IA) lipopolysaccharide (LPS) induces intrauterine and fetal lung inflammation and increases lung surfactant and compliance in preterm sheep; however, the mechanisms are unknown. Prostaglandins (PGs) are inflammatory mediators, and PGE2 has established roles in fetal lung surfactant production. The aim of our first study was to determine PGE2 concentrations in response to IA LPS and pulmonary gene expression for PG synthetic [prostaglandin H synthase-2 (PGHS-2) and PGE synthase (PGES)] and PG-metabolizing [prostaglandin dehydrogenase (PGDH)] enzymes and PGE2 receptors. Our second study aimed to block LPS-induced increases in PGE2 with a PGHS-2 inhibitor (nimesulide) and determine lung inflammation and surfactant protein mRNA expression. Pregnant ewes received an IA saline or LPS injection at 118 days of gestation. In study 1, fetal plasma and amniotic fluid were sampled before and at 2, 4, 6, 12, and 24 h after injection and then daily, and fetuses were delivered 2 or 7 days later. Amniotic fluid PGE2 concentrations increased (P 0.05) 12 h and 3–6 days after LPS. Fetal lung PGHS-2 mRNA and PGES mRNA increased 2 (P 0.0084) and 7 (P 0.014) days after LPS, respectively. In study 2, maternal intravenous nimesulide or vehicle infusion began immediately before LPS or saline injection and continued until delivery 2 days later. Nimesulide inhibited LPS-induced increases in PGE2 and decreased fetal lung IL-1 and IL-8 mRNA (P 0.002) without altering lung inflammatory cell infiltration. Nimesulide decreased surfactant protein (SP)-A (P 0.05), -B (P 0.05), and -D (P 0.0015) but increased SP-C mRNA (P 0.023). Thus PGHS-2 mediates, at least in part, fetal pulmonary responses to inflammation.
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